title: Male-female differences in the genetic regulation of t-PA and PAI-1 levels in a Ghanaian population.
abstract: Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) directly influence thrombus formation and degradation, and have been identified as risk factors for thromboembolic disease. Prior studies investigated determinants of t-PA and PAI-1 expression, but mainly in Caucasian subjects. The aim of this study was to identify the contributions of genetic and other factors to inter-individual variation in plasma levels of t-PA and PAI-1 in a large-scale population-based sample from urban West Africa. t-PA, PAI-1 and several demographic, anthropometric, and metabolic parameters were measured in 992 residents of Sunyani, the capital of the Brong-Ahafo region of Ghana. In addition, nine gene polymorphisms associated with components of the renin-angiotensin and fibrinolytic systems were determined. We found that BMI, systolic and diastolic blood pressure, total cholesterol, glucose, and triglycerides were all significant predictors of t-PA and PAI-1 in both females and males. In addition, a significant relationship was found between the PAI-1 4G/5G (rs1799768) polymorphism on PAI-1 levels in females, the TPA I/D (rs4646972) polymorphism on t-PA and PAI-1 in males, the renin (rs3730103) polymorphism on t-PA and PAI-1 in males, the ethanolamine kinase 2 (rs1917542) polymorphism on PAI-1 in males, and the renin (rs1464816) polymorphism on t-PA in females and on PAI-1 in males. This study of urban West Africans shows that t-PA and PAI-1 levels are determined by both genetic loci of the fibrinolytic and renin-angiotensin systems and other factors often associated with cardiovascular disease, and that genetic factors differ between males and females.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical School, Nashville, TN, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Schoenhard
authors.forename: F W
authors.initials: FW
authors.lastname: Asselbergs
authors.forename: K A
authors.initials: KA
authors.lastname: Poku
authors.forename: S A
authors.initials: SA
authors.lastname: Stocki
authors.forename: S
authors.initials: S
authors.lastname: Gordon
authors.forename: D E
authors.initials: DE
authors.lastname: Vaughan
authors.forename: N J
authors.initials: NJ
authors.lastname: Brown
authors.forename: J H
authors.initials: JH
authors.lastname: Moore
authors.forename: Scott M
authors.initials: SM
authors.lastname: Williams
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D005260:Female; D005342:Fibrinolysis / Q000235:genetics; D005869:Ghana; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000235:genetics*; D011110:Polymorphism, Genetic; D012084:Renin-Angiotensin System / Q000235:genetics; D012727:Sex Characteristics; D010959:Tissue Plasminogen Activator / Q000097:blood* / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D014280:Triglycerides; D002784:Cholesterol; D010959:Tissue Plasminogen Activator